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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Friedrich, Jana, et al.
(författare)
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Investigating hypoxia in aquatic environments: diverse approaches to addressing a complex phenomenon
- 2014
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 11, s. 1215-1259
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we provide an overview of new knowledge on oxygen depletion (hypoxia) and related phenomena in aquatic systems resulting from the EU-FP7 project HYPOX (“In situ monitoring of oxygen depletion in hypoxic ecosystems of coastal and open seas, and landlocked water bodies”, www.hypox.net). In view of the anticipated oxygen loss in aquatic systems due to eutrophication and climate change, HYPOX was set up to improve capacities to monitor hypoxia as well as to understand its causes and consequences. Temporal dynamics and spatial patterns of hypoxia were analyzed in field studies in various aquatic environments, including the Baltic Sea, the Black Sea, Scottish and Scandinavian fjords, Ionian Sea lagoons and embayments, and Swiss lakes. Examples of episodic and rapid (hours) occurrences of hypoxia, as well as seasonal changes in bottom-water oxygenation in stratified systems, are discussed. Geologically driven hypoxia caused by gas seepage is demonstrated. Using novel technologies, temporal and spatial patterns of watercolumn oxygenation, from basin-scale seasonal patterns to meter-scale sub-micromolar oxygen distributions, were resolved. Existing multidecadal monitoring data were used to demonstrate the imprint of climate change and eutrophication on long-term oxygen distributions. Organic and inorganic proxies were used to extend investigations on past oxygen conditions to centennial and even longer timescales that cannot be resolved by monitoring. The effects of hypoxia on faunal communities and biogeochemical processes were also addressed in the project. An investigation of benthic fauna is presented as an example of hypoxia-devastated benthic communities that slowly recover upon a reduction in eutrophication in a system where naturally occurring hypoxia overlaps with anthropogenic hypoxia. Biogeochemical investigations reveal that oxygen intrusions have a strong effect on the microbially mediated redox cycling of elements. Observations and modeling studies of the sediments demonstrate the effect of seasonally changing oxygen conditions on benthic mineralization pathways and fluxes. Data quality and access are crucial in hypoxia research. Technical issues are therefore also addressed, including the availability of suitable sensor technology to resolve the gradual changes in bottom-water oxygen in marine systems that can be expected as a result of climate change. Using cabled observatories as examples, we show how the benefit of continuous oxygen monitoring can be maximized by adopting proper quality control. Finally, we discuss strategies for state-of-the-art data archiving and dissemination in compliance with global standards, and how ocean observations can contribute to global earth observation attempts.
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- Rennie, JM, et al.
(författare)
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Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: a multicentre experience
- 2019
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Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 104:5, s. F493-F501
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres.MethodsNeonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server.ResultsOf 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9–51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11–32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED.ConclusionsOur results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat.Oberservation study numberNCT02160171
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